The importance of autoplastically transplanted pituitaries for survival and for regeneration of adultTriturus

Résumé Une hypophyse greffée autoplastiquement dans la chambre antérieure de l'il, dans lemanus ou dans letarsus s'est avérée capable de remplacer l'hypophysein situ dans son action sur la régénération et la survie chez le Triton, à condition que s'établisse une vascularisation satisfaisante du greffon et que la durée de l'expérience ne dépasse pas plusieurs mois.     

Carcinostatic activity of a thiazolidinonylidene-hydrazonothiazolidinone derivative against DMBA-induced mammary carcinomata in female Sprague-Dawley rats

Zusammenfassung 5-Methyl-3-(2-methylallyl)-2-[(3-methyl-4-oxo-2-thiazolidinyliden)-hydrazono]-4-thiazolidinon erwies sich bei guter therapeutischer Breite als stark karzinostatisch wirksam bei DMBA-induzierten Mamma-Karzinomen weiblicher Sprague-Dawley Ratten. Eine geringere chemotherapeutische Wirkung fand sich auch bei Walker CaSa 256, DMBA-induzierten Hautkarzinomen und Ehrlich Ascites Karzinom.     

Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death

Mutations in ion channels involved in the generation and termination of action potentials constitute a family of molecular defects that underlie fatal cardiac arrhythmias in inherited long-QT syndrome. We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters, causes dominantly inherited type 4 long-QT cardiac arrhythmia in humans. Mice heterozygous for a null mutation in ankyrin-B are haploinsufficient and display arrhythmia similar to humans. Mutation of ankyrin-B results in disruption in the cellular organization of the sodium pump, the sodium/calcium exchanger, and inositol-1,4,5-trisphosphate receptors (all ankyrin-B-binding proteins), which reduces the targeting of these proteins to the transverse tubules as well as reducing overall protein level. Ankyrin-B mutation also leads to altered Ca2+ signalling in adult cardiomyocytes that results in extrasystoles, and provides a rationale for the arrhythmia. Thus, we identify a new mechanism for cardiac arrhythmia due to abnormal coordination of multiple functionally related ion channels and transporters.     

Break-up of the Atlantic deep western boundary current into eddies at 8 degrees S

The existence in the ocean of deep western boundary currents, which connect the high-latitude regions where deep water is formed with upwelling regions as part of the global ocean circulation, was postulated more than 40 years ago. These ocean currents have been found adjacent to the continental slopes of all ocean basins, and have core depths between 1,500 and 4,000 m. In the Atlantic Ocean, the deep western boundary current is estimated to carry (10-40) x 10(6) m3 s(-1) of water, transporting North Atlantic Deep Water--from the overflow regions between Greenland and Scotland and from the Labrador Sea--into the South Atlantic and the Antarctic circumpolar current. Here we present direct velocity and water mass observations obtained in the period 2000 to 2003, as well as results from a numerical ocean circulation model, showing that the Atlantic deep western boundary current breaks up at 8 degrees S. Southward of this latitude, the transport of North Atlantic Deep Water into the South Atlantic Ocean is accomplished by migrating eddies, rather than by a continuous flow. Our model simulation indicates that the deep western boundary current breaks up into eddies at the present intensity of meridional overturning circulation. For weaker overturning, continuation as a stable, laminar boundary flow seems possible.     

Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide-modified liposomes

Protein transduction domains (PTDs) are used to enhance cellular uptake of drugs, proteins, polynucleotides or liposomes. In this study, functionalized Antennapedia (Antp, aa 43–-58) and HIV Tat (aa 47–57) peptides were coupled to small unilamellar liposomes via thiol-maleimide linkage. Modified liposomes showed higher uptake into a panel of cell lines including tumor and dendritic cells than unmodified control liposomes. Liposome uptake was time and concentration dependent as analyzed by flow cytometry and live-cell microscopy. At least 100 PTD molecules per small unilamellar liposome (100 ± 30 nm) were necessary for efficient translocation into cells. Cellular uptake of PTD-modified liposomes was 15- to 25-fold increased compared to unmodified liposomes and was inhibited by preincubation of liposomes with heparin. Glycosaminoglycan-deficient CHO cells showed dramatically reduced cell association of PTD-modified liposomes, confirming the important role of heparan sulfate proteoglycans in PTD-mediated uptake. Antp-liposomes used as carriers of the cytotoxic drug N⁴-octadecyl-1--D-arabinofuranosylcytosine-(5- 5)-3-C-ethinylcytidine showed a reduction of the IC₅₀ by 70% on B16F1 melanoma cells compared with unmodified liposomes. PTD-functionalized liposomes, particularly Antp-liposomes, represent an interesting novel carrier system for enhanced cell-specific delivery of a large variety of liposome-entrapped molecules.Received 16 April 2004; received after revision 13 May 2004; accepted 25 May 2004